Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We differentiate (continuing the scheme of the National Wilms' Tumor Study) three groups of Wilms' tumors (WT), which for practical reasons also encompass WT variants: 1. a group of low-grade malignant tumors comprising 9.3% of cases (congenital mesoblasticnephroma; cystic, partially differentiated nephroblastoma); 2. the main group of tumors with histologically standard malignancy and constituting 77.7% of cases, against which a combined therapy is used depending upon age and stage of spread; and 3. a small group of tumors of high-grade malignancy (anaplastic WT, clear cell sarcoma of the kidney; malignant rhabdoid tumor of the kidney). This latter group constitutes only 13% of cases but is responsible for a high percentage of total deaths due to WT. To the tumor group with standard malignancy belong the classic triphasic WT (without anaplasia) as well as WT "with quantitative deviations", in which either the blastemic, the epithelial, or the stroma component dominates. In the differential diagnosis the relatively frequent blastemic WT must be differentiated from other so-called small, round, and blue cell tumors of childhood, especially the undifferentiated neuroblastomas. Pseudo-rosettes and cytokeratin expression are signs of an "early" epithelial differentiation. Anaplastic WT (comprising 6.1% of our cases) are diagnosed according to the criteria of BECKWITH and PALMER (1978). They are aneuploid tumors and occur predominantly in children over two years of age. By contrast, the histogenetic still undefined clear cell sarcomas and malignant rhabdoid tumors of the kidney occur chiefly in children under two. Both tumors are diploid, notwithstanding their high-grade malignancy. Clear cell sarcoma, which contains a high content of vessels and comprises 3.7% of our cases, consists of cells with weakly stained and partially vacuolized cytoplasm. In contrast to normal WT, clear cell sarcoma often progresses to bone metastases. Malignant rhabdoid tumor (2.7% of our cases) possesses cells with large, roundish nuclei, pale chromatin, very prominent nucleoli and characteristic spherical intermediate filament condensations. Cross striation and myoglobin are never present. Malignant rhabdoid tumor is not a genuine kidney tumor; it may also occur extrarenally. Low-grade congenital mesoblastic nephroma is a spindel cell tumor often exhibiting high cellularity and characterized by fingerlike projections extending into the adjacent kidney tissue. Nephroblastomatosis, with preferential perilobular localization, is a potential WT precursor found in 25% to 40% of all nephrectomy specimens containing WT and in all cases of bilateral and multifocal WT. Nevertheless, only a small proportion of the usually very small "nephrogenic remnants" lead by way of an adenomatous proliferation to manifestation of WT.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[New aspects of nephroblastoma (Wilms tumor) and other metanephrogenic neoplasms]. 248 20

Metastases from prostatic adenocarcinoma (prostate cancer) are characterized by their predilection for bone and typical osteoblastic features. An in vitro model of bone metastases from prostate cancer was developed using a bicompartment coculture system of mouse osteoblasts and human prostate cancer cells. In this model, the bone-derived prostate cancer cell lines MDA PCa 2a and MDA PCa 2b induced a specific and reproducible increase in osteoblast proliferation. Moreover, these cells were able to induce osteoblast differentiation, as assessed by increased alkaline phosphatase activity, Osteocalcin expression, and calcified matrix formation. This osteoblastic reaction was confirmed in vivo by intrafemoral injection of MDA PCa 2b cells into severe combined immunodeficiency disease mice. In contrast, the highly undifferentiated, bone-derived human prostate cancer cell line PC3 did not produce an osteoblastic reaction in vitro and induced osteolytic lesions in vivo. The osteoblast differentiation induced by MDA PCa 2b cells was associated with up-regulation of the osteoblast-specific transcriptor factor Cbfa1. Moreover, treatment of osteoblasts with conditioned medium obtained from MDA PCa 2b cells resulted in up-regulation of Cbfa1 and Osteocalcin expression. In support of the differentiation studies, a microarray analysis showed that primary mouse osteoblasts grown in the presence of MDA PCa 2b cells showed a shift in the pattern of gene expression with an increase in mRNA-encoding Procollagen type I and Osteopontin and a decrease in mRNA-encoding proteins associated with myoblast differentiation, namely myoglobin and myosin light-chain 2. Taken together, these findings suggest that the bone-derived prostate cancer cells MDA PCa 2a and MDA PCa 2b promote differentiation of osteoblast precursors to an osteoblastic phenotype through a Cbfa1-dependent pathway. These results also established that soluble factors produced by prostate cancer cells can induce expression of osteoblast-specific genes. This in vitro model provides a valuable system to isolate molecules secreted by prostate cancer cells that favor osteoblast differentiation. Moreover, it allows to screen for therapeutic agents blocking the osteoblast response to prostate cancer.
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PMID:Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent pathway. 1145 20